Selective resynchronization therapy optimization based on user preference

ABSTRACT

A method and system for calculating an atrio-ventricular delay interval based upon an inter-atrial delay exhibited by a patient&#39;s heart. The aforementioned atrio-ventricular delay interval may optimize the stroke volume exhibited by a patient&#39;s heart. The aforementioned atrio-ventricular delay interval may be blended with another atrio-ventricular delay interval that may optimize another performance characteristic, such as left ventricular contractility. Such blending may include finding an arithmetic mean, geometric mean, or weighted mean of two or more proposed atrio-ventricular delay intervals.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.11/109,603, now issued as U.S. Pat. No. 7,613,514, filed Apr. 19, 2005,which is hereby incorporated by reference in its entirety.

TECHNICAL FIELD

This present invention relates to cardiac rhythm management devicesgenerally, and more particularly to cardiac pacing systems that employan atrio-ventricular delay based in part upon a measured inter-atrialdelay.

BACKGROUND

FIG. 1 depicts a human heart 100. As can be seen from FIG. 1, the heart100 includes four chambers, the right and left atria 102 and 104,respectively, and the right and left ventricles 106 and 108,respectively. The heart 100 pumps so as to circulate blood through thehuman body in the following manner. Blood flows from the peripheralvenous system to the right atrium 102. From the right atrium 102, bloodpasses through the tricuspid valve 110 to the right ventricle 106. Bloodexits the right ventricle 106 through the pulmonary artery and isdirected through the lungs, so that the blood may be reoxygenated.Oxygenated blood from the lungs is drawn from the pulmonary vein to theleft atrium 104. From the left atrium, blood passes though the mitralvalve 112 to the left ventricle 108. Finally, the blood flows from theleft ventricle 108, through the aortic valve, to the peripheral arterialsystem in order to transfer oxygenated blood to the organs of the body.

To cause the blood to circulate in the above-described manner,electrical pulses propagate through the heart 100, causing the variouscardiac muscle cells to contract when excited by the pulses. Usually,the cycle of electrical excitation of the heart 100 is initiated by thesinoatrial node 114. An electrical impulse is generated by thesinoatrial node 114. The impulse propagates from the sinoatrial node 114to the right and left atria 102 and 104. As a consequence of normalpropagation, the right and left atria 102 and 104 contract atsubstantially the same time. Contraction of the atria 102 and 104 forceblood from the right and left atria 102 and 104 into the right and leftventricles 106 and 108, respectively. Eventually, the electrical impulsereaches the atrioventricular node 116. From the atrioventricular node116, the electrical impulse is carried along right and left bundlebranch fibers (not depicted) to a network of fast-conducting Purkinjefibers (not depicted) that extend throughout most of the endocardialsurface of the ventricles 106 and 108. The ventricles 106 and 108, whenexcited by the electrical impulse, contract at substantially the sametime, causing the blood therein to exit and travel to either the lungsor the peripheral arterial system, as mentioned above.

Efficiency of heart function may be influenced by several factors.Amongst those factors is synchrony between the chambers of the heart.Efficient heart function is encouraged by atrio-ventricular synchrony,meaning that the ventricles 106 and 108 should contract shortly aftercontraction of the atria 102 and 104. Premature ventricular contractionmay lead to inefficiency because the ventricles 106 and 108 do notbecome fully filled with blood before contraction. On the other hand,retarded ventricular contraction may permit some of the blood containedin the ventricles 106 and 108 to flow back into the atria 102 and 104prior to ventricular contraction—an effect that is also inimical toefficient heart function.

Efficient heart function is also encouraged by interventricularsynchrony. The right and left ventricles 106 and 108 share a wall incommon, the septum 118. Should the right ventricle 106 contract prior tocontraction of the left ventricle 108, the septum 118 may initiallycontract with the right ventricle 106, shifting to the right. Then, uponcontraction of the left ventricle 108, the septum 118 may contract withthe left ventricle 108, and shift to the left. Thus, the septum 118 mayexhibit a sort of “waffling” action, shifting first to the right andthen to the left. Such waffling yields an inefficient cardiac stroke.

To encourage proper synchrony amongst the ventricles 106 and 108 oratria 102 and 104, cardiac resynchronization therapy may be employed bya cardiac rhythm management device, such as a pacemaker or defibrillatorwith pacing capabilities. Herein, the terms pacemaker, pulse generatordevice, and cardioverter/defibrillator (with pacing functionality) areused interchangeably and refer to a cardiac rhythm management device.Cardiac resynchronization therapy involves pacing one or both ventricles106 and 108 in order to synchronize their contraction with one anotheror with one or both of the atria 102 and 104.

One important variable governing cardiac resynchronization therapy is anatrio-ventricular pacing delay interval that is employed by the deviceapplying the resynchronization therapy. As explained in more detail,below, the atrio-ventricular pacing delay interval is responsible fordetermining the timing of pacing of one or both of the ventriclesrelative to a paced or sensed event occurring in the right atrium 102.

In atrial tracking and AV sequential pacing modes, a ventricular escapeinterval is defined between atrial and ventricular events. This escapeinterval is the aforementioned atrio-ventricular pacing delay intervalor AVD interval, where a ventricular pacing pulse is delivered uponexpiration of the atrio-ventricular pacing delay interval if noventricular sense occurs before such expiration. In an atrial trackingmode, the atrio-ventricular pacing delay interval is triggered by anatrial sense and stopped by a ventricular sense or pace. An atrialescape interval can also be defined for pacing the atria either alone orin addition to pacing the ventricles. In an AV sequential pacing mode,the atrio-ventricular delay interval is triggered by an atrial pace andstopped by a ventricular sense or pace. Atrial tracking and AVsequential pacing are commonly combined so that the AVD interval startswith either an atrial pace or sense.

SUMMARY OF THE INVENTION

Against this backdrop, the present invention was developed. A method ofarriving at a blended atrio-ventricular delay value may include thefollowing acts. A first atrio-ventricular delay value selected toapproximately maximize contractility of a ventricle may be determined.Next, a second atrio-ventricular delay value selected to approximatelymaximize stroke volume of the ventricle may be determined. Finally, thefirst and second atrio-ventricular delay values may be combined.

According to another embodiment, a system may include a cardiac rhythmmanagement device. The system may also include a first lead having anelectrode configured to make electrical contact with a region in theright atrium of a heart. The first lead may be configured to be coupledto the cardiac rhythm management device. The system may also include asecond lead having an electrode configured to pass through andelectrically contact the mid-coronary sinus of the heart beforeelectrically contacting a left ventricle of the heart. The second leadmay be configured to be coupled to the cardiac rhythm management device.Finally, the system may include a programmer configured to communicateddata with the cardiac rhythm management device. The programmer includesinstructions that perform a mode of operation, during which, signalsfrom the second lead are interpreted as indicating left atrial activity,and upon termination of the mode of operation, signals from the secondlead are interpreted as indicating left ventricular activity. Theinter-atrial delay is determined by finding a span of time separating apaced or sensed event in the right atrium and a signal from the secondlead indicating left atrial activity.

According to another embodiment a method of implanting a cardiac rhythmmanagement device may include implanting a first lead so that anelectrode therein makes electrical contact with a region within a rightatrium of a heart. Next, a second lead is implanted so that a firstelectrode thereof makes electrical contact with the mid-coronary sinusof the heart and a second electrode thereof makes electrical contactwith a first region of a left ventricle of the heart. Finally, the firstand second leads are coupled to a cardiac rhythm management device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a human heart.

FIG. 2 depicts a chart relating changes in aortic pulse pressure to arange of AVD intervals.

FIG. 3 depicts a chart relating changes in positive-going rates ofchange of left ventricular pressure over a range of AVD intervals.

FIG. 4 depicts a scheme for determining inter-atrial delay, according toone embodiment of the present invention.

FIG. 5 depicts a programmer in communication with a pulse generatordevice.

FIG. 6 depicts a mode of operation that may be invoked for measuringinter-atrial delay.

FIG. 7A depicts a lead for sensing the left atrium, according to oneembodiment of the present invention.

FIG. 7B depicts another lead for sensing the left atrium, according toone embodiment of the present invention.

FIG. 8 depicts a pulse generator device that is an example of a suitableenvironment for incorporation of the methods, schemes, and leadsdisclosed herein.

DETAILED DESCRIPTION

Heart function efficiency may be characterized in different ways,including characterization according to the left ventricularcontractility or according to stroke volume. Briefly, left ventricularcontractility indicates the capacity of the ventricular to contract(i.e., to squeeze, and therefore to force blood through the peripheralarterial system). Stroke volume, on the other hand, measures the volumeof blood passing through the aorta (and to the peripheral arterialsystem), with each stroke of the heart.

In some instances, it is possible that one particular AVD intervaloptimizes a given patient's heart function, as understood by leftventricular contractility, while another AVD interval optimizes thatpatient's heart function, as understood by stroke volume. For instance,a patient may exhibit a cardiac condition wherein propagation ofelectrical impulses from the right atrium 102 to the left atrium 104 isdramatically slowed. For example, in an ordinary heart, such propagationmay transpire over a time interval on the order of 30-50 milliseconds,while a defective heart may exhibit a propagation time on the order of100-200 milliseconds. In a heart exhibiting such a condition, the rightatrium 102 contracts prior to contraction of the left atrium 104.Consequently, blood exits the right atrium 102 and fills the rightventricle 106, prior to blood exiting the left atrium 104 and fillingthe left ventricle 108. In such a circumstance, it may be desirable toemploy an AVD interval of sufficient length to ensure that the leftventricle 108 has an opportunity to fill with blood prior tocontraction. By permitting the left ventricle 108 to fill with bloodprior to contraction, it stands to reason that a relatively largervolume of blood should be forced from the left ventricle upon itscontraction. Thus, it is possible that stroke volume is improved ormaximized by employment of such an AVD interval. An AVD intervalachieving the such a goal is a function of the inter-atrial propagationdelay, or any signal or physiological event in predictable relation tothe inter-atrial propagation delay. In other words,AVD_(stroke volume)=f(inter-atrial delay),where AVD_(stroke volume) represents an AVD interval maximizing strokevolume for a given patient and lead configuration or pacing chamber.

On the other hand, a heart may exhibit a condition known as left bundlebranch block. In such a heart, the right ventricle 106 contracts priorto contraction of the left ventricle 108. As described above, this mayresult in a waffling action of the septum 118. To alleviate thiscondition, a device may employ an AVD interval that causes bothventricles 106 and 108 to contract at a point time no later than that atwhich the right ventricle 106 would have intrinsically contracted. Bycapturing both ventricles 106 and 108, and causing them to contractsubstantially simultaneously, the waffling action of the septum 118 maybe inhibited, thereby enhancing the overall contractility of the leftventricle. Such an AVD interval is a function of the propagation delaysbetween the right atrium 102 and the right and left ventricles 106 and108, or any signal or physiological event in predictable relation tosuch delays. In other words,AVD_(contractility)=f(RA−RV,RA−LV),where AVD_(contractility) represents an AVD interval maximizing leftventricular contractility for a given patient and lead configuration orpacing chamber, RA-RV represents a time interval during which anelectrical impulse propagates between the right atrium and the rightventricle, and RA-LV represents a time interval during which anelectrical impulse propagates between the right atrium and the leftventricle.

The discussion (below) relating to FIGS. 2 and 3 presents dataconsistent with the notion that, for a given patient and pacing chamber,the AVD interval at which left ventricular contractility is maximizeddiffers from that at which stroke volume is maximized.

Stroke volume is generally understood to correspond to aortic pulsepressure. Thus, for a given patient and pacing chamber, one may programa device to employ a range of AVD intervals and measure the resultingaortic pulse pressure. The AVD interval at which the maximum aorticpulse pressure is observed corresponds to the AVD interval at which themaximum stroke volume would be observed, if directly measured. In otherwords, aortic pulse pressure may be measured as a surrogate for strokevolume.

FIG. 2 depicts a chart 200 relating changes in aortic pulse pressure toa range of AVD intervals. The chart 200 is constructed from averageddata obtained over a populace of patients. Percent change in aorticpulse pressure is plotted along the y-axis. The AVD interval is plottedalong the x-axis. As can be seen, the maximum positive change in aorticpulse pressure occurs at an AVD interval of about 80 milliseconds.Therefore, according to the chart 200 of FIG. 2, AVD_(stroke volume)=80ms for the particular populace of patients and pacing chamber used incollecting the data presented therein.

Left ventricular contractility is generally understood to correspond tothe positive-going change in left ventricular pressure per unit of time(denoted LV+dP/dt). Thus, for a given patient and pacing chamber, onemay program a device to employ a range of AVD intervals, and may measurethe resulting positive-going change in left ventricular pressure perunit of time. The AVD interval at which the maximum positive-goingchange in left ventricular pressure per unit of time is observedcorresponds to the AVD interval at which the maximum left ventricularcontractility would be observed, if directly measured. In other words,positive-going change in left ventricular pressure per unit of time maybe measured as a surrogate for left ventricular contractility.

FIG. 3 depicts a chart 300 relating changes in positive-going rates ofchange of left ventricular pressure over a range of AVD intervals. Likethe chart 200 of FIG. 2, the chart 300 of FIG. 3 is constructed fromaveraged data obtained from the same populace of patients used incollecting the data presented in FIG. 2. Percent change in thepositive-going rate of change of left ventricular pressure is plottedalong the y-axis. The AVD interval is plotted along the x-axis. As canbe seen, the maximum change in the positive-going rate of change of leftventricular pressure occurs at an AVD interval of about 150milliseconds. Therefore, according to the chart 300 of FIG. 3,AVD_(contractility)=150 ms for the particular populace of patients andpacing chamber used in collecting the data presented therein.

From FIGS. 2 and 3, it can be seen thatAVD_(stroke volume)≠AVD_(contractility) for the particular populace ofpatients used to generate the data presented in those figures. Moreover,these figures suggest that the optimal AVD intervals for maximizingpulse pressure and LV+dP/dt may differ within an individual.

The implication of the data presented in FIGS. 2 and 3 is that aphysician, when configuring a cardiac resynchronization therapeuticdevice for a patient, is faced with a choice: either configure thedevice to use an AVD interval intended to maximize stroke volume, orconfigure the device to use an AVD interval intended to maximize leftventricular contractility. Among other thins, the present inventors haverecognized that one approach for resolving this dilemma is to presentthe physician with a range of intermediate AVD intervals betweenAVD_(stroke volume) and AVD_(contractility). Thus, for example, aphysician may be presented with an option to select an AVD interval thatis a weighted average of AVD_(stroke volume) and AVD_(contractility).This approach is discussed in further detail, below.

Using the raw data presented in FIG. 2, it has been determined thatAVD_(stroke volume) may be arrived at, for a given patient and leadconfiguration/pacing chamber, by the following formula:AVD_(stroke volume) =K ₁*IAD+K ₂,where K₁ and K₂ are constants, and IAD represents the inter-atrial delayexhibited by a given patient's heart. Other formulas forAVD_(stroke volume) are also suitable, such as those described in U.S.Pat. No. 6,144,880, which is incorporated by reference in its entirety,including such description.

The above-recited formula for AVD_(stroke volume) is a function ofinter-atrial delay. The inter-atrial delay exhibited by a heart may varybased upon whether the electrical impulse originated intrinsically(e.g., originated at the sinoatrial node), or originated from a pacinglead (i.e., the right atrium was paced). Thus, AVD_(stroke volume) maybe calculated separately for each source of origination—one such delayinterval to follow an atrial sense and one delay interval to follow anatrial pace.

In one embodiment, the constants K₁ and K₂ in the above-recited formulaare: K₁=1.22, and K₂=−133 milliseconds. Values for K₁ and K₂ areapproximate and may vary. Further, these value may vary from patient topatient, and may vary with time. Still further, these values may varywith lead placement and/or pacing mode. Further yet, these values mayvary as a function of conduction disorder type. All such variations arewithin the scope of the present invention.

The above-recited formula for AVD_(stroke volume) requires measurementof the inter-atrial delay exhibited by a particular patient's heart.Many techniques to acquire the inter-atrial delay are known and arewithin the scope of the present invention. Some of the known techniquesinvolve the use of equipment that is not normally present in theelectrophysiology lab at the time of implantation of a pulse generatordevice. For the sake of convenience, it may be desirable to obtain theinter-atrial delay data using equipment that is normally present at thetime of implantation. The following discussion presents schemes thatpermit the acquisition of the inter-atrial delay using equipmentnormally present at the time of implantation.

Ordinarily, one or more leads extend from a pulse generator into one ormore of the various chambers of a patient's heart. Usually, the lead(s)gain entry into the heart by way of passing through the superior venacava. For example, in the context of a pectoral implantation of a pulsegenerator device, a lead may be inserted into the subclavian vein andextended through that vein into the superior vena cava, whereupon thelead enters the right atrium of the heart. One or more electrodes on thelead used to pace and sense the right atrium are then implanted in theright atrium.

The lead used for pacing and sensing the right ventricle is advancedthrough the right atrium, and threaded through the tricuspid valve intothe right ventricle. Again, one or more electrodes on the lead used topace and sense the right ventricle are then implanted in therein.

To reach the left ventricle, a lead is advanced through the rightatrium, and extended into the coronary sinus. Next, the left ventricularlead is threaded through the coronary sinus, and into the leftventricle. Then, one or more electrodes on the lead are implanted in theleft ventricle.

While the left ventricular lead is advanced through the coronary sinus,an opportunity for sensing electrical activity in the left atriumemerges. Specifically, the left ventricular lead may be advanced to aposition where the electrode(s) thereon are located at about themid-coronary sinus. When the electrodes are located at about themid-coronary sinus, they are physically located along a peripheralregion of the left atrium, meaning that an electrical signal propagatingthrough the left atrium may be detected. During implantation, thephysician may halt the advancement of the left ventricular lead when theelectrodes are at the aforementioned location. Then, the leftventricular lead may be used to detect electrical activity in the leftatrium.

To obtain the inter-atrial delay, the physician may follow the proceduredescribed by FIG. 4. As shown in FIG. 4, a lead is implanted in theright atrium in the standard manner (operation 400), and the leftventricular lead is placed at the mid-coronary sinus, as discussed above(operation 402). Thereafter, the right atrial lead may be used to paceor sense an event in the right atrium, as shown in operation 404. Then,the ensuing left atrial event is sensed using the left ventricular lead(operation 406). Finally, the span of time separating the paced orsensed event in operation 404 and the sensed event in operation 406 ismeasured, yielding an inter-atrial delay measurement at operation 408.

Because a patient's heart may exhibit different inter-atrial delaysdepending upon whether the right atrial event is paced or sensed,operations 404 through 408 may be performed once for a paced even andonce for a sensed event. (Operations 404-408 may be performed amultiplicity of times for a paced event, and a multiplicity of times fora sensed event. The data resulting from operations 404-408 for each ofthe paced events may be averaged, to arrive at an average inter-atrialdelay exhibited in the wake of a paced event. Similarly, the dataresulting from operations 404-408 for each of the sensed events may beaveraged, to arrive at an average inter-atrial delay exhibited in thewake of a sensed event.)

During implantation of a pulse generator, operation 406 may be aided bya programmer unit. By way of background, during an implantationprocedure, a physician may make use of a programmer unit 500, asdepicted in FIG. 5. The programmer unit 500 may be a general-purposecomputer, having a peripheral board (not depicted) that supportstelemetry functionality. The programmer unit 500 communicates with apulse generator device 502 by way of a telemetry wand 504 that is drivenby the aforementioned peripheral board.

The programmer unit 500 may query the pulse generator 502 regarding itspacing parameters, for example. The programmer unit 500 may also commandthe pulse generator to perform certain actions, such as pace aparticular chamber when a button is selected by the user of theprogrammer unit 500.

The programmer unit 500 may be programmed to provide an automatic schemefor measuring the inter-atrial delay. During implantation, the physicianmay invoke the automatic scheme, causing the programmer unit 500 tocommand the pulse generator device 502 to enter a mode of operation inwhich the acts depicted in FIG. 6 are executed. During the mode ofoperation, the pulse generator device 502 interprets the signalsemanating from its left ventricular lead as indicating left atrialactivity, as opposed to indicating left ventricular activity (operation600). The pulse generator 502 may either await a sensed event from theright atrial lead, or may pace the right atrium (operation 602). Thepaced or sensed event in the right atrium is recorded and time-stampedby the pulse generator 502 (operation 602). Alternatively, the pulsegenerator device 502 may activate a timer upon occurrence of the pacedor sensed event in the right atrium. Next, as shown in operation 604,the pulse generator device 502 awaits a sensed event in the left atrium(the event is detected via the left ventricular lead, as discussedpreviously). The sensed event in the left atrium is recorded andtime-stamped by the pulse generator device 502 (operation 604).Alternatively, if the pulse generator device 502 had activated a timerduring execution of operation 602, the timer may be halted duringexecution of operation 604. Finally, as shown in operation 606, thetime-stamps recorded in operations 602 and 604 are returned to the pulsegenerator device 502. Alternatively, if a timer wasactivated/deactivated in lieu of recording and time-stamping the atrialevents, the value of the timer may be returned to the programmer unit500. Thus, in sum, the effect of operations 600-606 is to measure a spanof time separating a paced or sensed event in the right atrium from theensuing sensed event in the left atrium. In the wake of operation 606having been performed, the pulse generator device 502 may return tointerpreting signals emanating from the left ventricular lead asindicating left ventricular activity.

As an alternative, the programmer unit 500 may command the pulsegenerator unit 502 to stream real-time electrogram data or event markersto the programmer while the electrode(s) of the left ventricular leadare situated at about the mid-coronary sinus. Then, the programmer unit500, instead of the pulse generator device 502, may execute operations600-604. In other words, the programmer unit 500 may interpret theelectrogram data or event markers in a manner such that signalsemanating from the left ventricular lead are interpreted as indicatingleft atrial activity, instead left ventricular activity (operation 600).The programmer unit 500 awaits an indication in the electrogram data orevent marker data of a sensed event in the right atrium, or commands apaced event therein (operation 602). Thereafter, the programmer unit 500awaits an indication in the electrogram data or event marker data of asensed left atrial event (operation 604). The programmer unit 500 findsthe inter-atrial delay by measuring the time interval separating theevents of operations 602 and 604, such as by starting/stopping a timer.

There exists yet another scheme by which a patient's inter-atrial delaymay be determined. The scheme involves the use of a lead 700, depictedin schematic form in FIG. 7A. The lead 700 depicted in FIG. 7A includesa tip electrode 704 and a ring electrode 702. The tip electrode 704 andring electrode 702 are separated by a distance d₁. The distance d₁between the tip and ring electrodes 704 and 702 is of sufficient lengththat the ring electrode 702 may be situated at approximately themid-coronary sinus, while the tip electrode 704 is placed within theleft ventricle (e.g., left ventricular free wall or left ventricularanterior wall).

During implantation, the lead 700 of FIG. 7A may be extended through themid-coronary sinus to the left ventricle, as discussed above. The tipand ring electrodes 704 and 702 may be implanted in the left ventricleand mid-coronary sinus, respectively. During operation, each electrode702 and 704 operates in a unipolar mode (i.e., sense and pace to the“can” electrode of the pulse generator device). Thus, given such anarrangement, the ring electrode 702 may be used to sense electricalactivity in the left atrium. The ring electrode 702 senses such activityin a unipolar mode. Additionally, the tip electrode 704 may be used tosense and pace the left atrium. Again, the tip electrode 704 senses andpaces in a unipolar mode.

Use of the lead 700 depicted in FIG. 7A permits the inter-atrial delayexhibited by a heart to be measured with each atrial event, if desired.With the occurrence of each such event, the pulse generator device 502may measure the span of time between the sensed or paced event in theright atrium and the subsequent sensed event in the left atrium. Thus, apulse generator device 502 using the lead 700 of FIG. 7A may recalculateAVD_(stroke volume) with each paced or sensed event, or at designatedintervals.

As an alternative to the lead 700 of FIG. 7A, the lead 706 of FIG. 7Bmay be used. The lead 706 of FIG. 7B includes a tip electrode 708 andtwo ring electrodes 710 and 712. The tip electrode 708 and first ringelectrode 710 are in proximity to one another, as are an ordinarytip/ring electrode pair. The tip 708 and ring 710 electrode pair may beused for pacing and sensing the left ventricle. Thus, pacing and sensingin the left ventricle may be performed in a bipolar mode (between tipand ring) or in a unipolar mode. As can be seen from FIG. 7B, the secondring electrode 712 is separated from the first ring electrode by adistance d₂. The distance d₂ between the first and second ringelectrodes 710 and 712 is of sufficient length that the second ringelectrode 712 may be situated at approximately the mid-coronary sinus,while the first ring electrode is placed within the left ventricle(e.g., left ventricular free wall or left ventricular anterior wall).

During implantation, the lead 706 of FIG. 7B may be extended through themid-coronary sinus to the left ventricle, as discussed above. The tip708 and ring 710 electrode pair may be implanted in the left ventricle,while the second ring electrode 712 may be implanted in the mid-coronarysinus. As mentioned above, during operation, the tip 708 and ring 710electrode pair may operate in bipolar or unipolar mode. The second ringelectrode 712 operates in a unipolar mode. Thus, given such anarrangement, the second ring electrode 712 may be used to senseelectrical activity in the left atrium. The second ring electrode 712senses such activity in a unipolar mode.

Use of the lead 706 depicted in FIG. 7B permits the inter-atrial delayexhibited by a heart to be measured with each atrial event, if desired.With the occurrence of each such event, the pulse generator device 502may measure the span of time between the sensed or paced event in theright atrium and the subsequent sensed event in the left atrium. Thus, apulse generator device 502 using the lead 706 of FIG. 7B may recalculateAVD_(stroke volume) with each paced or sensed event, or at designatedintervals.

Returning to the previous discussion of FIG. 3, based upon the raw datapresented therein, it has been determined that AVD_(contractility) maybe arrived at, for a given patient and lead configuration by thefollowing formula:AVD_(contractility) =K ₃ *QRS+K ₄ *AVR+K ₅,where K₃, K₄, and K₅ are constants, QRS represents the width of the QRScomplex, and AVR represents the span of time separating a paced orsensed right atrial event and a sensed right ventricular event.

The above-recited formula for AVD_(contractility) is a function of thespan of time separating a paced or sensed right atrial event and asensed right ventricular event. It is also a function of the width ofthe QRS complex. As stated previously, for a given heart, theseparticular spans of time may vary based upon whether the electricalimpulse originated intrinsically (e.g., originated at the sinoatrialnode), or originated from a pacing lead (i.e., the right atrium waspaced). Thus, AVD_(contractility) may be calculated separately for eachsource of origination-one such delay interval to follow an atrial senseand one delay interval to follow an atrial pace.

The constants K₃, K₄ and K₅ in the above-recited formula may vary basedupon lead placement. Thus, for example, when pacing only the leftventricle with a left ventricular anterior wall lead placement,K₃=−1.325, K₄=0.918, and K₅=135.3. When performing biventricular pacingwith a left ventricular anterior wall lead placement, K₃=−0.835,K₄=1.041, and K₅=49. When pacing only the left ventricle with a leftventricular free wall lead placement, K₃=−0.459, K₄=0.911, and K₅=−4.3.Finally, when performing biventricular pacing with left ventricular freewall lead placement, K₃=−0.728, K₄=0.757, and K₅=71.3. Values for K₃, K₄and K₅ are approximate and may vary. Further, these values may vary frompatient to patient, and may vary with time. Still further, these valuesmay vary with lead placement and/or pacing mode. Further yet, thesevalues may vary as a function of conduction disorder type. All suchvariations are within the scope of the present invention.

When the span of time separating a paced or sensed right atrial eventand a sensed left ventricular event (AVL) can be measured accurately,the following equation for AVD_(contractility) may be used:AVD_(contractility) =K ₆ *AVL+K ₇ *AVR+K ₈,where K₆, K₇, and K₈ are constants, AVR represents the span of timeseparating a paced or sensed right atrial event and a sensed rightventricular event, and AVL represents the span of time separating apaced or sensed right atrial event and a sensed left ventricular event.Other formulas for AVD_(contractility) are also suitable, such as thosedescribed in U.S. Pat. No. 6,144,880, which is incorporated by referenceherein in its entirety, including such description.

The above-recited formula for AVD_(contractility) is a function of thespan of time separating a paced or sensed right atrial event and asensed right ventricular event. It is also a function of the span oftime separating a paced or sensed right atrial event and a sensed leftventricular event. For a given heart, these particular spans of time mayvary based upon whether the electrical impulse originated intrinsically(e.g., originated at the sinoatrial node), or originated from a pacinglead (i.e., the right atrium was paced). Thus, AVD_(contractility) maybe calculated separately for each source of origination—one such delayinterval to follow an atrial sense and one delay interval to follow anatrial pace.

The constants K₆, K₇ and K₈ in the above-recited formula may vary basedupon lead placement. Thus, for example, when pacing only the leftventricle with a left ventricular anterior wall lead placement,K₆=0.163, K₇=0.769, and K₈=−59.6. When performing biventricular pacingwith a left ventricular anterior wall lead placement, K₆=0.063,K₇=1.008, and K₈=−73. When pacing only the left ventricle with a leftventricular free wall lead placement, K₆=−0.099, K₇=0.988, and K₈=−64.3.Finally, when performing biventricular pacing with a left ventricularfree wall lead placement, K₆=−0.126, K₇=0.857, and K₈=−27.5. Values forK₆, K₇ and K₈ are approximate and may vary. Further, these value mayvary from patient to patient, and may vary with time. Still further,these values may vary with lead placement and/or pacing mode. Furtheryet, these values may vary as a function of conduction disorder type.All such variations are within the scope of the present invention.

The preceding discussion has presented various schemes and formulas forarriving at AVD_(contractility) and AVD_(stroke volume). Other schemesmay be employed for arriving at AVD intervals designed to optimizeperformance characteristics other than stroke volume and leftventricular contractility. What follows is a discussion of variousmethods for blending AVD_(contractility) and AVD_(stroke volume). Byblending AVD_(contractility) and AVD_(stroke volume), it may be possibleto arrive at an AVD interval that yields improved or optimal cardiacefficiency for left ventricular contractility and stroke volume,considered as a whole. The following blending schemes may be used toblend any set of calculated AVD intervals—not just AVD_(contractility)and AVD_(stroke volume).

One scheme for blending AVD_(contractility) and AVD_(stroke volume) isto find the arithmetic mean of the two figures:AVD_(blended)=(AVD_(contractility)+AVD_(stroke volume))/2,where AVD_(blended) represents an AVD interval that is the result ofblending AVD_(contractility) and AVD_(stroke volume). This calculationmay be executed by the pulse generator device 502 or the programmer unit500.

Another scheme for blending AVD_(contractility) and AVD_(stroke volume)is to find the geometric mean of the two figures:AVD_(blended)=[(AVD_(contractility))(AVD_(stroke volume))]^(1/2).Again, this scheme may be performed by the pulse generator device 502 orthe programmer unit 500.

Yet another scheme for blending AVD_(contractility) andAVD_(stroke volume) is to find a weighted average of the two figures:AVD_(blended)=(K ₅*AVD_(contractility) +K ₆*AVD_(stroke volume))/(K ₅ +K₆),where K₅ and K₆ are coefficients that determine the relative weight withwhich each of AVD_(contractility) AVD_(stroke volume) are blendedtogether.

A programmer unit 500 may be programmed to permit a physician to entervalue for K₅ and K₆, so that the physician can determine the relativeimportance of each performance variable. For example, a physician mayuse the programmer unit 500 in the following manner. The programmer unitmay present each of the proposed AVD interval values, i.e.,AVD_(contractility) and AVD_(stroke volume). Upon inspect of theproposed AVD interval values, the physician may enter weight values tobe applied to AVD_(contractility) and AVD_(stroke volume). For example,the physician may use the programmer unit 500 to select a weight of “8”for stroke volume, and a weight of “2” for contractility. Accordingly,the AVD_(stroke volume) is given four times the weight given toAVD_(contractility) in blending the two figures together. Again, theactual calculations may be performed by the pulse generator device 502or the programmer unit 500.

What follows is an exemplary embodiment of a pulse generator device thatmay be used to employ any of the aforementioned schemes, and may be usedwith any of the aforementioned leads and lead configurations. Of course,other embodiments of pulse generator devices and are within the scope ofthe present invention, if employing any of the aforementioned schemesand lead configurations disclosed here.

A block diagram of a multi-site pacemaker having multiple sensing andpacing channels is shown in FIG. 8. (As the term is used herein, a“pacemaker” should be taken to mean any cardiac rhythm managementdevice, such as an implantable cardioverter/defibrillator, with a pacingfunctionality.) The controller of the pacemaker is made up of amicroprocessor 800 communicating with a memory 802 via a bidirectionaldata bus, where the memory 802 typically comprises a ROM (read-onlymemory) for program storage and a RAM (random-access memory) for datastorage. The controller could be implemented by other types of logiccircuitry (e.g., discrete components or programmable logic arrays) usinga state machine type of design, but a microprocessor-based system ispreferable. As used herein, the programming of a controller should betaken to refer to either discrete logic circuitry configured to performparticular functions or to the code executed by a microprocessor. Thecontroller is capable of operating the pacemaker in a number ofprogrammed modes where a programmed mode defines how pacing pulses areoutput in response to sensed events and expiration of time intervals. Atelemetry interface 804 is also provided for communicating with anexternal programmer.

The embodiment shown in FIG. 8 has three sensing/pacing channels, wherea pacing channel is made up of a pulse generator connected to anelectrode while a sensing channel is made up of the sense amplifierconnected to an electrode. A switching network 806 controlled by themicroprocessor is used to switch the electrodes from the input of asense amplifier to the output of a pulse generator. The switchingnetwork 806 also allows the sensing and pacing channels to be configuredby the controller with different combinations of the availableelectrodes. The channels may be configured as either atrial orventricular channels, allowing the device to deliver conventionalventricular single-site pacing with or without atrial tracking,biventricular pacing, or multi-site pacing of a single chamber. In anexample configuration, a right atrial sensing/pacing channel includesring electrode 808 a and tip electrode 808 b of bipolar lead 808 c,sense amplifier 810, pulse generator 812, and a channel interface 814. Aright ventricular sensing/pacing channel includes ring electrode 816 aand tip electrode 816 b of bipolar lead 816 c, sense amplifier 818,pulse generator 820, and a channel interface 822, and a left ventricularsensing/pacing channel includes ring electrode 824 a and tip electrode824 b of bipolar lead 824 c, sense amplifier 826, pulse generator 828,and a channel interface 830. The channel interfaces communicatebi-directionally with a port of microprocessor 800 and includeanalog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers, registers that can be written to for adjustingthe gain and threshold values of the sensing amplifiers, and registersfor controlling the output of pacing pulses and/or changing the pacingpulse amplitude. In this embodiment, the device is equipped with bipolarleads that include two electrodes which are used for outputting a pacingpulse and/or sensing intrinsic activity. Other embodiments may employunipolar leads with single electrodes for sensing and pacing. Theswitching network 806 may configure a channel for unipolar sensing orpacing by referencing an electrode of a unipolar or bipolar lead withthe device housing or can 832.

The controller 800 controls the overall operation of the device inaccordance with programmed instructions stored in memory. The controller800 interprets electrogram signals from the sensing channels andcontrols the delivery of paces in accordance with a pacing mode. Thesensing circuitry of the pacemaker generates atrial and ventricularelectrogram signals from the voltages sensed by the electrodes of aparticular channel. When an electrogram signal in an atrial orventricular sensing channel exceeds a specified threshold, thecontroller detects an atrial or ventricular sense, respectively, whichpacing algorithms may employ to trigger or inhibit pacing. Anelectrogram is analogous to a surface ECG and indicates the time courseand amplitude of cardiac depolarization that occurs during either anintrinsic or paced beat.

Embodiments of the invention may be implemented in one or a combinationof hardware, firmware, and software. Embodiments of the invention mayalso be implemented as instructions stored on a machine-readable medium,which may be read and executed by at least one processor to perform theoperations described herein. A machine-readable medium may include anymechanism for storing or transmitting information in a form readable bya machine (e.g., a computer). For example, a machine-readable medium mayinclude read-only memory (ROM), random-access memory (RAM), magneticdisc storage media, optical storage media, flash-memory devices,electrical, optical, acoustical or other form of propagated signals(e.g., carrier waves, infrared signals, digital signals, etc.), andothers.

The Abstract is provided to comply with 37 C.F.R. Section 1.72(b)requiring an abstract that will allow the reader to ascertain the natureand gist of the technical disclosure. It is submitted with theunderstanding that it will not be used to limit or interpret the scopeor meaning of the claims.

In the foregoing detailed description, various features are occasionallygrouped together in a single embodiment for the purpose of streamliningthe disclosure. This method of disclosure is not to be interpreted asreflecting an intention that the claimed embodiments of the subjectmatter require more features than are expressly recited in each claim.Rather, as the following claims reflect, inventive subject matter liesin less than all features of a single disclosed embodiment. Thus, thefollowing claims are hereby incorporated into the detailed description,with each claim standing on its own as a separate preferred embodiment.

1. A system comprising: a sensing circuit configured to: (1) detect atleast one of a sensed or paced atrial event; and (2) detect a sensedventricular event; and a controller or programmer circuit, configured tobe communicatively coupled to the sensing circuit, the controller orprogrammer circuit configured to: (1) determine a measuredatrioventricular delay (AVD) concluded by the sensed ventricular event;(2) determine a measured interatrial delay (IAD) concluded by the sensedatrial event; (3) determine a first atrioventricular delay value, AVD₁,selected to approximately maximize contractility of a ventricle, usingthe measured AVD concluded by the sensed ventricular event; and (4)determine a second atrioventricular delay value, AVD₂, selected toapproximately maximize stroke volume of the ventricle, using themeasured IAD concluded by the sensed atrial event, wherein thecontroller or programmer circuit is configured to use a blendedatrioventricular delay (AVD_(blended)) that is determined using auser-modifiable function of both AVD₁ and AVD₂, wherein theAVD_(blended) is determined as an individually-scaled sum of AVD₁ andAVD₂.
 2. The system of claim 1, wherein the controller or programmercircuit includes, or is configured to be communicatively coupled to, auser interface configured to receive user input and communicate outputinformation to a user.
 3. The system of claim 2, wherein the userinterface is configured to receive user input including a firstcoefficient K₅ to be applied to AVD₁ and a second coefficient K₆ to beapplied to AVD₂; and wherein the controller or programmer circuit isconfigured to determine the blended atrioventricular delay according toAVD_(blended)=(K₅*AVD₁+K₆* AVD₂)/(K₅+K₆).
 4. The system of claim 2,wherein the user interface is configured to communicate an indication ofat least one of AVD₁, or AVD₂, or AVD_(blended) to a user.
 5. The systemof claim 1, comprising: a first lead, configured to be communicativelycoupled to the sensing circuit and the controller or programmer circuit,the first lead having an electrode configured to make electrical contactwith a region in a right atrium of a heart; and a second lead,configured to be communicatively coupled to the sensing circuit and thecontroller or programmer circuit, the second lead having an electrodeconfigured to pass through and electrically contact a mid-coronary sinusof the heart before electrically contacting a left ventricle of theheart; wherein the controller or programmer circuit is configured toperform a mode of operation, during which, a signal from the second leadis interpreted as indicating left atrial activity, and upon terminationof the mode of operation, a signal from the second lead is interpretedas indicating left ventricular activity; and wherein the controller orprogrammer circuit is configured to determine the IAD during the mode ofoperation using a time interval between a paced or sensed event in theright atrium, indicated by a signal from the first lead, and a sensedevent in the left atrium, indicated by a signal from the second lead. 6.The system of claim 5, comprising a third lead, configured to becommunicatively coupled to the sensing circuit and the controller orprogrammer circuit, the third lead having an electrode configured tomake electrical contact with a region within a right ventricle of theheart; wherein the controller or programmer circuit is configured todetermine the AVD upon termination of the mode of operation using, atleast in part, a time interval between a paced or sensed event in theright atrium, indicated by a signal from the first lead, and a sensedevent in the left ventricle, indicated by a signal from the second lead;and wherein the controller or programmer circuit is also configured todetermine the AVD using, at least in part, a time interval between apaced or sensed event in the right atrium, indicated by a signal fromthe first lead, and a sensed event in the right ventricle, indicated bya signal from the third lead.
 7. The system of claim 5, wherein thecontroller or programmer circuit includes, or is configured to becommunicatively coupled to, a user interface configured to permit a userof the controller or programmer circuit to initiate the mode ofoperation.
 8. The system of claim 1, wherein the ventricle is the leftventricle, and wherein peak positive left ventricular pressure change isused as a measurable indicator of contractility of the left ventricle.9. The system of claim 1, wherein aortic pulse pressure is used as ameasurable indicator of stroke volume.
 10. The system of claim 1,wherein the controller or programmer circuit is configured to determineAVD₁ using, at least in part, a time interval between a paced or sensedevent in the right atrium and a sensed event in a right ventricle; andwherein the controller or programmer circuit is also configured todetermine AVD₁ using, at least in part, a time interval between a pacedor sensed event in the right atrium and a sensed event in the leftventricle.
 11. The system of claim 10, wherein the controller orprogrammer circuit is configured to determine AVD₁ using the formulaAVD₁=K₁*AVR+K₂*AVL, wherein K₁ is a constant, AVR represents the timeinterval between a paced or sensed event in the right atrium and asensed event in the right ventricle, K₂ is a constant, and AVLrepresents the time interval between a paced or sensed event in theright atrium and a sensed event in the left ventricle.
 12. The system ofclaim 1, wherein the controller or programmer circuit is configured todetermine AVD₂ using, at least in part, a time interval between a pacedor sensed event in the right atrium and a sensed event in the leftatrium.
 13. The system of claim 12, wherein the controller or programmercircuit is configured to determine AVD₂ using the formulaAVD₂=K₃*IAD+K₄, wherein K₃ is a constant, IAD represents the timeinterval between the paced or sensed event in the right atrium and thesensed event in the left atrium, and K₄ is a constant.
 14. The system ofclaim 1, comprising a pacing circuit configured to be programmed by thecontroller or programmer circuit to provide cardiac electrostimulationpulses according to AVD_(blended).
 15. The system of claim 1, whereinthe controller or programmer circuit is configured to determine AVD₁using a detected right atrial pace or sensed depolarization and adetected mid-coronary sinus left ventricular pace or senseddepolarization.
 16. The system of claim 1, wherein the controller orprogrammer circuit is configured to determine the IAD by measuring atime interval between a paced or sensed event in the right atrium and asignal indicating left atrial activity; and wherein the controller orprogrammer is configured to use the IAD to determine AVD_(blended). 17.The system of claim 1, wherein the controller or programmer circuit isconfigured to determine AVD₁ using at least one of: (1) a function of atime interval, AVR, between a paced or sensed event in the right atriumand a sensed event in the right ventricle; or (2) a function of a timeinterval, AVL, between a paced or sensed event in the right atrium and asensed event in the left ventricle.
 18. The system of claim 1, whereinthe controller or programmer circuit is configured to determine AVD₁using a function of a QRS width.
 19. The system of claim 18, wherein thecontroller or programmer circuit is configured to determine AVD₁ usingthe equation AVD₁=K₃*QRS+K₄*AVR+K₅, wherein K₃, K₄, and K₅ areconstants, QRS represents the width of the QRS complex, and AVRrepresents a time interval between a paced or sensed right atrial eventand a sensed right ventricular event.
 20. A system comprising: a sensingcircuit configured to: (1) detect at least one of a sensed or pacedatrial event; and (2) detect a sensed ventricular event; and acontroller or programmer circuit, configured to be communicativelycoupled to the sensing circuit, the controller or programmer circuitconfigured to: (1) determine a measured atrioventricular delay (AVD)concluded by the sensed ventricular event; (2) determine a measuredinteratrial delay (IAD) concluded by the sensed atrial event; (3)determine a first atrioventricular delay value, AVD₁, selected toapproximately maximize contractility of a ventricle, using the measuredAVD concluded by the sensed ventricular event; and (4) determine asecond atrioventricular delay value, AVD₂, selected to approximatelymaximize stroke volume of the ventricle, using the measured IADconcluded by the sensed atrial event, wherein the controller orprogrammer circuit is configured to use a blended atrioventricular delay(AVD_(blended)) that is determined using a user-weightable function ofboth AVD₁ and AVD₂; a pacing circuit configured to be programmed by thecontroller or programmer circuit to provide cardiac electrostimulationpulses according to AVD_(blended); and wherein the AVD_(blended) isdetermined according to AVD_(blended)=(K₅* AVD₁+K₆*AVD₂)/(K₅+K₆).